In accordance with paragraph 8 of Section IV of the Procedure for Expert Evaluation, the applicant must amend the instructions for medical use of the medicinal product upon receipt of new data, including bringing the instructions for medical use into line with the approved instructions for medical use of the original (reference) medicinal product, and ensure that the information on the medicinal product corresponds to current scientific knowledge.
The previous publication is available on the website of the State Expert Center of the Ministry of Health of Ukraine at the following links:
https://www.dec.gov.ua/materials/zminy-informacziyi-z-bezpeky-likarskyh-zasobiv-shho-mistyat-pemetreksed-pemetrexed-za-rezultatamy-zasidannya-komitetu-z-oczinky-ryzykiv-u-farmakonaglyadi-prac-vid-30-veresnya-3-zhovtnya/?role=applicant
https://www.dec.gov.ua/materials/zminy-informacziyi-z-bezpeky-likarskyh-zasobiv-shho-mistyat-pemetreksed-pemetrexed-za-rezultatamy-zasidannya-komitetu-z-oczinky-ryzykiv-u-farmakonaglyadi-prac-vid-30-veresnya-3-zhovtnya-2/?role=doctors
The Pharmacovigilance Risk Assessment Committee (PRAC), based on the analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing pemetrexed, PSUSA/00002330/202402, made the following conclusions.
Given the available data on the pharmacokinetics of pemetrexed and taking into account that in vitro studies indicate its active secretion via organic anion transporter 3 (OAT3), as well as the IC50 values for proton pump inhibitors, the PRAC considers that a drug interaction between proton pump inhibitors and pemetrexed is at least reasonably possible. The PRAC concluded that the package inserts of medicinal products containing pemetrexed should be amended accordingly.
Having considered the PRAC recommendations, the Committee for Medicinal Products for Human Use (CHMP) agrees with the overall conclusions of the PRAC and the grounds for the recommendations.
Based on the scientific conclusions regarding pemetrexed, the CHMP considers that the benefit/risk balance of medicinal products containing pemetrexed remains unchanged, subject to the proposed changes being made to the instructions for medical use.
Changes to be made to the relevant sections of the package leaflets (new text is underlined and in bold deleted text is struck through).
- Section "Interaction with other medicinal products and other forms of interaction"
The following changes should be made to the interaction(s):
Pemetrexed is eliminated primarily unchanged by the kidneys through tubular secretion and, to a lesser extent, through glomerular filtration. Concomitant use of nephrotoxic medicinal products (e.g., aminoglycosides, loop diuretics, platinum compounds, cyclosporine) may potentially lead to delayed clearance of pemetrexed. This combination should be used with caution. If necessary, creatinine clearance should be closely monitored.
Concomitant use of pemetrexed with OAT3 (organic anion transporter) inhibitors of substances that are also eliminated by tubular secretion (for example, probenecid, penicillin, proton pump inhibitors) may potentially lead to delayed clearance of pemetrexed. Caution should be exercised when using these medicinal products concomitantly with pemetrexed. If necessary, creatinine clearance should be monitored closely.
Pemetrexed is eliminated by tubular secretion via the human organic anion transporter 3 (hOAT3). Caution should be exercised when pemetrexed is co-administered with proton pump inhibitors or other hOAT3 inhibitors.
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List of medicinal products containing pemetrexed that are authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 03.02.2025).
TO ANALYZE THE PUBLISHED INFORMATION AND SUBMIT THE CORRESPONDING APPLICATION FOR AMENDMENTS TO THE REGISTRATION MATERIALS, THE APPLICANT MUST USE THE ORIGINAL TEXT POSTED AT THE LINKS:
